Heterocyclicacetonitriles and fungicidal use

ABSTRACT

A class of novel heterocyclicacetonitriles which is useful in the control of fungi, especially bitunicate asci and unitunicate asci, has been discovered. These compounds are of the general formula: ##STR1## wherein Ar 1  and Ar 2  are substituted or unsubstituted aryl groups; Het is a six-membered nitrogen-containing heterocyclic ring; n is the integer 2 or 3; and the agronomically acceptable enantiomorphs, acid addition salts and metal complexes thereof.

STATUS OF RELATED APPLICATIONS

This is a divisional of U.S. Ser. No. 08/152,555 filed on Nov. 15, 1993,now U.S. Pat. No. 5,397,793; is a continuation of U.S. Ser. No.07/491,782 filed on Mar. 12, 1990, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to novel heterocyclicacetonitrile derivatives,and enantiomorphs, salts and metal salt compIexes thereof and their useas broad spectrum fungirides.

2. Description of the Prior Art

Taylor, et al., U.S. Pat. Nos. 3,818,009; 3,868,244, and 3,887,708,describe a series of alpha-disubstituted-5-pyrimidine methanes which areuseful as plant growth regulators and fugicides. They prepared onecyanide compound: α,α-diphenyl-(5-pyrimidyl)acetonitrile. Taylor andHolden, U.S. Pat. No. 3,544,682, disclose a fungitidal method employingsubstituted pyrazines. In the course of this workα,α-diphenyl-pyrazinyl-acetonitrile was claimed as a fungicide.

Van Heyrdnagen and Taylor, U.S. Pat. No. 3,397,273 disclose a broadclass of 3-pyridyl methane derivatives as fungicides. Nitrile compoundsare disclosed, but no specific examples were made or tested.

Katritzky, et al., I. Chem. Eng. Data 1987, 32, 479-481 prepared certainpyrazinyl compounds of this invention for evaluation as herbicides.There is no teaching that these compounds would be active as fungiddes.

SUMMARY OF THE INVENTION

A class of novel heterocyclicacetonitriles which is useful in thecontrol of fungi, especially those with bitunicate asd and urdtunicateasci, has been discovered. These compounds are of the general formula:##STR2## wherein Ar₁ is a substituted or unsubstituted aryl group; Ar₂is a substituted or unsubstituted aryl group or thiopheneyl or furanylgoup; Het is a six-membered nitrogen-containing heterocyclic ring; n isthe integer 2 or 3; and the agronomically acceptable enantiomorphs, acidaddition salts and metal-complexes thereof.

This invention also teaches methods of preparing this new class ofcompounds as well as methods of using the compounds as fungicides.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to fungicidal compounds of the general formula Iwherein Ar₁ is selected from an optionally substituted C₆ to C₁₀ arylgroup with up to three substituents independently selected from thegroup consisting of halogen, nitro, cyano, (C₁ -C₁₂) alkyl, (C₁ -C₁₂)haloalkyl, (C₃ -C₈) cycloalkyl, (C₅ -C₈) cycloalkenyl, (C₂ -C₁₂)alkenyl, (C₂ -C₁₂) alkynyl, (C₁ -C₁₂) alkoxy, (C₁ -C₁₂) haloalkoxy, (C₁-C₁₂) alkylthio, (C₁ -C₁₂) alkylsulfinyl, (C₁ -C₁₂) alkylsulfonyl,phenyl, phenoxy, phen(C₁ -C₁₂)alkyl, phen(C₂ -C₁₂)alkenyl, phen(C₂-C₁₂)alkynyl and (C₅ -C₆)cydoalkyl (C₁ -C₆)alkyl; Ar₂ is an optionallysubstituted (C₆ -C₁₀) aryl group wherein the substituents areindependently selected from the substituents enumerated above for Ar₁ ;or Ar₂ may be thiopheneyl or furanyl; Het is a six membered heterocyclicring consisting of 3 to 5 carbon atoms and 1 to 3 nitrogen atoms; n isthe integer 1, 2 or 3; and the agronomically acceptable enantiomorphs,add addition salts and metal complexes thereof; and with the provisothat when Het is pyrazinyl and n is two then Ar₁ and Ar₂ cannot both bephenyl.

Compounds possessing substantially the same properties as theunsubstituted phenyl and phenoxy substituents defined by the formulaabove, which can be prepared in the same manner and are equivalentsthereof are those wherein the phenyl or phenoxy group bears one or moresimple substituents, including but not limited to, lower alkyl, halogenand lower alkoxy.

The term "aryl" as used in the present specification and claims means anaromatic ring structure of 6 to 10 carbon atoms, preferably a phenyl ornaphthyl group which may be unsubstituted or optionally substituted withup to three substituents, preferably with one substituent, selected fromthe group consisting of halogen, nitro, cyano, (C₁ -C₁₂) alkyl, (C₃ -C₈)cydoalkyl, (C₁ -C₁₂) haloalkyl, (C₁ -C₁₂) alkoxy, (C₂ -C₁₂) alkenyl, (C₃-C₈) cycloalkenyl, (C₂ -C₁₂) alkynyl, (C₁ -C₁₂) alkylthio, (C₁ -C₁₂)alkylsulfinyl, (C₁ -C₁₂) alkylsulfonyl, phenyl, phen (C₁ -C₁₂) alkyl,phen (C₂ -C₁₂) alkenyl, phen (C₂ -C₁₂) alkynyl and (C₅ -C₆) cycloalkyl(C₁ -C₆) alkyl.

Typical aryl groups encompassed by this invention are phenyl, naphthyl,2, 4-dichlorophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-nitrophenyl,4-fluorophenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4-bromophenyl,3-chlorophenyl, 3-fluorophenyl, 4-bromophenyl, 4-biphenyl,2-fluorophenyl, 2-chlorophenyl, 2-cyanonaphthyl, 4-chloronaphthyl and4-methylthiophenyl, 4-phenoxyphenyl, and4-(2',4'-dichlorophenoxy)phenyl.

By the term "Het" as used in the present specification and claims meansa six-membered heterocyclic ring consisting of three to five carbonatoms and one to three nitrogen atoms. Examples of heterocyclic ringsencompassed by this invention are 2-pyridyl, 3-pyridyl, 4-pyridyl,3-pyridyl N-oxide, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, pyrazinyl,3-pyridazinyl, 4-pyridazinyl and triazenyl.

The term "alkyl" as used in defining the substituents on the aromaticgroups in the present specification and claims means both straight andbranched carbon chains from one to twelve atoms.

The term "pestidally or fungicidally effective amount" means a quantityof compound which causes a reduction of the pest or fungus population ordecreases crop damage as compared to a control group.

The term "agronomically acceptable carrier" means a solid or liquidwhich is biologically, chemically, and physically compatible with thecompounds of this invention.

A preferred embodiment of this invention is the compounds, salts andenantiomorphs represented by formula I wherein Ar₁ and Ar₂ areindependently selected from phenyl or phenyl substituted with up to twosubstituents selected from the group consisting of methyl, halomethyl,trihalomethyl halogen, and alkoxy; and Het is a six memberedheterocyclic ring consisting of 4 or five carbon atoms and 1 or 2nitrogen atoms; n is the integer 2 or 3; and agronomically acceptableenantiomorphs ,and add salts thereof.

A more preferred embodiment of this invention is the compounds, saltsand enantiomorphs represented by formula I wherein Ar₁ is unsubstitutedphenyl, or 2- or 4-halosubstituted phenyl; Ar₂ is unsubstituted phenylor 3- or 4-halosubstituted phenyl; Het is pyrazinyl, 3-pyridyl or5-pyrimidyl and n is the integer 2.

A still more preferred embodiment of this invention is the compoundssalts and enantiomorphs of formula I wherein Ar₁ is 2- or 4-chloro- orfluorophenyl; Ar₂ is 4-chloro- or 4-fluorophenyl; Het is 3-pyridyl or5-pyrimidyl; and n is the integer 2.

In another aspect, this invention relates to fungicidal compositionscomprising a fungicidally effective amount of the compounds,enantiomorphs, acid addition salts and metal complexes of formula I asdescribed above and an agronomically acceptable inert carrier.

In yet another aspect, this invention relates to a method of controllingfungi comprising contacting said fungi or the locus of said fungi with afungicidally effective amount of a compound of formula (Ia) as describedbelow: ##STR3## wherein Ar₁ is selected from an optionally substitutedC₆ to C₁₀ aryl group with up to three substituents independentlyselected from the group consisting of halogen, nitro, cyano, (C₁ -C₁₂)alkyl, (C₁ -C₁₂) haloalkyl, (C₃ -C₈) cydoalkyl, (C₅ -C₈) cycloalkenyl,(C₂ -C₁₂) alkenyl, (C₂ -C₁₂) alkynyl, (C₁ -C₁₂) alkoxy, (C₁ -C₁₂)haloalkoxy, (C₁ -C₁₂) alkylthio, (C₁ -C₁₂) alkylsulfinyl, (C₁ -C₁₂)alkylsulfonyl, phenyl, phenoxy, phen(C₁ -C₁₂)alkyl, phen(C₂-C₁₂)alkenyl, phen(C₂ -C₁₂)alkynyl and (C₅ -C₆)cydoalkyl (C₁ -C₆)alkyl;Ar₂ is an optionally substituted (C₆ -C₁₀) aryl group wherein thesubstituents are independently selected from the substituents enumeratedabove for Ar₁ ; or Ar₂ may be thiopheneyl or furanyl; Het is asix-membered nitrogen-containing heterocyclic ring; n is the integer 1,2 or 3; and the agronomically acceptable enantiomorphs, acid additionsalts and metal complexes thereof.

Compounds encompassed by the present invention include those illustratedin Table I.

                  TABLE I                                                         ______________________________________                                        Cpnd. Het         Ar.sub.1      Ar.sub.2 n                                    ______________________________________                                        A     5-Triazenyl 4-Octylphenyl 4-Trifluoro-                                                                           3                                                                    methylphenyl                                  B     5-Pyrimidyl 2-Ethoxynaphthyl                                                                            4-Allylphenyl                                                                          2                                    C     3-Pyridazinyl                                                                             1-Propargylnaphthyl                                                                         3-Propylthio-                                                                          3                                    2     phenyl                                                                  D     4-Pyriadazinyl                                                                            3-Dodecylphenyl                                                                             2-Cyclohexyl-                                                                          2                                                                    phenyl                                        E     4-Pyridyl   4-chloro-2-   2-Cyano-3-                                                                             3                                                      methoxyphenyl Nitrophenyl                                   F     2-Pyrimidyl 3-Propylsulfinyl-                                                                           3-Phenethyl-                                                                           2                                                      phenyl        phenyl                                        G     5-Pyrimidyl 4-(3'-Phenylbutene-                                                                         3-Methylsulf-                                                                          2                                                      2')-Phenyl    onylphenyl                                    H     Pyrazinyl   2,4-Dinitrophenyl                                                                           3-Cyano- 2                                                                    phenyl                                        I     2-Pyridyl   2,3,4-        3-Nitro-4-                                                                             3                                                      Tribromophenyl                                                                              Cyanophenyl                                   J     3-Pyridyl   3-(5'-phenylpentyne-                                                                        4-Cyclohexyl-                                                                          3                                                      1')-Phenyl    methylphenyl                                  K     4-Pyrimidyl 2-Chloro-5-   1-Cyano- 2                                                      Nitrophenyl   naphthyl-2                                    L     5-Pyrimidyl 4-Phenoxyphenyl                                                                             4-biphenyl                                                                             2                                    M     3-Pyridyl   4-(2',4'-     4-Trifluoro-                                                                           3                                                      Dichlorophenoxy)                                                                            methoxy-                                                        phenyl        phenyl                                        N     Pyrazinyl   4-(4'Chlorophenyl)-                                                                         4-Ethoxy-                                                                              2                                                      phenyl        phenyl                                        ______________________________________                                    

The heterocyclicacetonitriles of the present invention may be preparedby standard synthetic routes including the following preferredprocedures. ##STR4## Ar₁, Ar₂, Her and n are as defined above; X ischloro, bromo, methane sulfonate or p-toluene sulfonate.

Route 1 involves preparation of an alkylated benzylcyanide byconventional techniques, (See U.S. Pat. No. 4,366,165) thenincorporation of the heterocycle via alkylation with the chloro orbromoheterocycle, e.g., 3-bromopyridine or 5-bromopyrimidine.

This route is chosen when the side chain is phenethyl, phenpropyl. Theheterocydes used in route 1 include 3-pyridyl, 4-pyridyl, 5-pyrimidinyland pyrazinyl as the halo-heterocycle. However, with benzyl side chains,route 1 is sensitive to the heterocycle employed. With benzyl sidechains reaction with 3-bromopyridine results in loss of hydrocyanic acidand produces pyridyl ethylenes rather than the cyano product. With5-bromopyrirnidine the product can be either the cyano product or thepyrimidinyl ethylene depending on the time and temperature of thereaction.

The first step of route 1 may be conducted under phase transferconditions by alkylation of the appropriately substituted benzylcyanideswith about 1 to 2 equivalents of the appropriate phenylalkylhalide ormesylate or tosylate in the presence of a strong base such as sodium orpotassium hydroxide and a catalyst such as tetrabutylamonium bromidewith or without a solvent, preferably with a solvent such as toluene orchlorobenzene or a mixture thereof at temperatures of about 0° C. to100° C., preferably about 10° C. to 40° C.

Alternatively, the first step of route 1 may be conducted by alkylationof the appropriately substituted benzylcyanides using 1 or 2 equivalentsof arylalkylhalide in the presence of a strong base such as a metalhydroxide or hydride, e.g., sodium or potassium hydroxide or hydrideusing dimethylformarnide (DMF) or DMF/toluene or dimethylsulfoxide(DMSO) or DMSO/toluene as the solvent at temperatures of about 0° C. to100° C., preferably about 10° C. to 40° C.

The second step of Route 1 uses about 1.5 equivalents of a strong basesuch as sodium or potassium hydroxide or sodium or lithium amide orsodium or potassium hydride in a solvent such as DMF or DMSO and theappropriate halo substituted heterocycle at temperatures of about 0° to100° C., preferably about 75°-80° C. Route 1 is preferred for pyrimidinecompounds.

Reaction progress may be monitored by standard analytical proceduressuch as gas-liquid chrolomotography. The reactions are typicallycomplete in about 1-6 hours.

Route 1 has been used in the literature for the reaction ofdiphenylacetonitrile with 3-bromopyridine and 5-bromopyrimidine viasodium amide in liquid ammonia; see U.S. Pat. No. 3,818,009.

Route 1 is further illustrated in Examples 1, 2, 7 and 8. ##STR5##

Ar₁, Ar₂, Het and n are as defined above; X is chloro or bromo.

Route 2 incorporates the heterocycle during the initial step of thesynthesis and allows a convenient method for preparation of analogs. Inthe literature substitued benzyl cyanides have been reacted with3-bromopyridine and chloropyrazine. See Katritzky, et al., supra.Preparation using 3-bromopyridine have shown that powdered potassiumhydroxide in dimethyl sulfoxide and a 2 fold excess of 3-bromopyridinegives the initial alkylated intermediate 3 in moderate yields. It ispreferred to add the base to the nitrile and pyridine in contrast toperforming the anion. These distilled intermediates were coupled via ametal hydride or amide base, preferably sodium in dimethylformamide withphenethyl and phenpropyl bromides. Benzyl chlorides react rapidly andthis is the method of choice to prepare the benzyl side chainsespecially when the heterocycle is 3-pyridyl. For phenethyl andphenpropyl side chains the chloride, bromide or mesylate may serve asthe leaving group; bromide is preferred. In addition, the best resultsare obtained when the base such as sodium hydride (NaH) is added to theec-aryl pyridylacetonitrile intermediate and alkylating reagent, or thebase and alkylating reagent are premixed and the ec-phenyl pyridylacetonitrile is added. This is atypical to most types of alkylationemploying NaH.

The N-oxides can be prepared via oxidation for example withm-chloroperbenzoic add (MCPBA) in methylene chloride at 0° to 25° C.

Route 2 is further illustrated in Examples 3 and 4. Table II shows theroute of preparation and physical properties of a number of heterocyclicacetonitriles which exemplify this invention.

                  TABLE II                                                        ______________________________________                                         ##STR6##                                                                     Num-                                                                          ber   Y        X        Het     n   mp °C.                                                                        Route                              ______________________________________                                         1    H        4-Cl     Pyridyl-3                                                                             2   83-84  1                                   2    H        4-Cl     Pyrimidyl-5                                                                           2   89-91  1                                   3    H        4-Cl     Pyrimidyl-5                                                                           1    99-101                                                                              1                                   4    H        H        Pyridyl-3                                                                             2   70-73  1                                   5    H        H        Pyrimidyl-5                                                                           2   94-97  1                                   6    H        H        Pyrazinyl                                                                             2   90-93  1                                   7    H        2,4-Cl.sub.2                                                                           Pyrazinyl                                                                             1   81-83  1                                   8    3-Cl     4-F      Pyridyl-3                                                                             2   Oil    1                                   9    3-CF.sub.3                                                                             4-Cl     Pyridyl-3                                                                             2   Oil    1                                  10    3-F      4-Cl     Pyridyl-3                                                                             2   Oil    1                                  11    4-Cl     4-Cl     Pyridyl-3                                                                             2   Oil    1                                  12    2-F      4-Cl     Pyridyl-3                                                                             2   87-89  1                                  13    2-Cl     4-F      Pyridyl-3                                                                             2   89-91  1                                  14    2-Cl     4-F      Pyridyl-4                                                                             2   121-123                                                                              1                                  15    H        4-OCH.sub.3                                                                            Pyridyl-3                                                                             2   80-82  1                                  16    H        4-Cl     Pyrazinyl                                                                             2    99-101                                                                              1                                  17    H        4-Cl     Pyridyl-4                                                                             2    98-100                                                                              1                                  18    3-F      H        Pyridyl-4                                                                             1   133    1                                  19    4-F      3-Cl     Pyridyl-4                                                                             1   116-117                                                                              1                                  20    3-CF.sub.3                                                                             H        Pyridyl-4                                                                             1   118-119                                                                              1                                  21    4-F      4-Cl     Pyridyl-4                                                                             1   130-131                                                                              1                                  22    H        4-Cl     Pyridyl-3                                                                             1   109-111                                                                              2                                  23    H        4-Cl     Pyridyl-4                                                                             1   89-91  2                                  24    H        4-F      Pyridyl-3                                                                             1   93-95  2                                  25    H        4-CF.sub.3                                                                             Pyridyl-3                                                                             1   101-103                                                                              2                                  26    2-F      4-Cl     Pyridyl-3                                                                             1   119-121                                                                              2                                  27    2-F      4-CF.sub.3                                                                             Pyridyl-3                                                                             1    98-100                                                                              2                                  28    4-F      H        Pyridyl-3                                                                             2   Oil    2                                  29    4-F      4-Cl     Pyridyl-3                                                                             2   Oil    2                                  30    2-F      4-F      Pyridyl-3                                                                             2   86-88  1                                  31    4-Br     H        Pyridyl-3                                                                             2   Oil    1                                  32    3-Cl     H        Pyridyl-3                                                                             2   Oil    2                                  33    3-Cl     4-Cl     Pyridyl-3                                                                             2   109-111                                                                              1                                  34    3-Cl     2-F      Pyridyl-3                                                                             2   84-86  1                                  35    H        4-F      Pyridyl-3                                                                             2    98-100                                                                              2                                  36    2-F      3-Cl     Pyridyl-3                                                                             2   Oil    2                                  37    H        H        Pyrazinyl                                                                             1   71-73  2                                  38    H        4-Cl     Pyrazinyl                                                                             1    98-100                                                                              2                                  39    H        H        Pyridyl-3                                                                             1   136-138                                                                              2                                  40    H        H        Pyrimidyl-5                                                                           1   136-138                                                                              2                                  41    2-F      4-Cl     Pyrimidyl-5                                                                           2   86-88  1                                  42    2-F      4-Cl     Pyrazinyl                                                                             2   58-60  1                                  43    H        3-F      Pyridyl-3                                                                             2   83-85  2                                   44*  H        4-Cl     Pyridyl-3                                                                             2   169-171                                                                              2                                   45** H        4-Cl     Pyridyl-3                                                                             2   116-118                                                                              2                                  46    H        3-Br     Pyridyl-3                                                                             2   95-97  2                                  48    2-Cl     4-Cl     Pyrimidyl-5                                                                           2   122-123                                                                              1                                  49    2-F      4-F      Pyrimidyl-5                                                                           2   88-90  1                                  50    2Cl      4-F      Pyrimidyl-5                                                                           2   110-112                                                                              1                                  51    2-Cl     4-Cl     Pyrazinyl                                                                             2   101-103                                                                              1                                  52    2-F      4-F      Pyrazinyl                                                                             2   92-94  1                                  53    2-Cl     4-F      Pyrazinyl                                                                             2   108-110                                                                              1                                  54    2-Cl     4-Cl     Pyridyl-3                                                                             2   90-92  1                                  55    2-OCH.sub.3                                                                            4-Br     Pyrimidyl-5                                                                           2   117-118                                                                              1                                  56    2-OCH.sub.3                                                                            4-F      Pyrimidyl-5                                                                           2   102-104                                                                              1                                  57    H        4-Phenyl Pyridinyl-5                                                                           2   Oil    2                                  59    H        4-CH.sub.3                                                                             Pyridyl-3                                                                             2   Oil    1                                  60    H        4-CH.sub.3                                                                             Pyrimidyl-5                                                                           2   67-79  1                                  61    H        4-Cl     Pyridyl-3                                                                             3   Oil    1                                  62    H        4-Cl     Pyrimidyl-5                                                                           3   Oil    1                                  63    H        4-Cl     Pyrazinyl                                                                             3   Oil    1                                  67    H        4-Phenyl Pyrimidyl-5                                                                           1   Oil    1                                  68    H        4-Phenyl Pyrazinyl                                                                             1   Oil    1                                  ______________________________________                                         *nitrate salt of compound 1                                                   **sulfate salt of compound 1                                             

The heterocyclic acetonitriles, enantiomorphs, add addition salts andmetal salt complexes of the present invention are useful as agriculturalfungicides and as such can be applied to various lod such as the seed,the soil or the foliage. For such purposes these compounds can be usedin the technical or pure form as prepared, as solutions or asformulations. The compounds are usually taken up in a carrier or areformulated so as to render them suitable for subsequent dissemination asfungirides. For example, these chemical agents can be formulated aswettable powders, emulsifiable concentrates, dusts, granularformulations, aerosols, or flowable emulsion concentrates. In suchformulations, the compounds are extended with a liquid or solid carrierand, when desired, suitable surfactants are incorporated.

It is usually desirable, particularly in the case of foliar sprayformulations, to include adjuvants, such as wetting agents, spreadingagents, dispersing agents, stickers, adhesive and the like in accordancewith agricultural practices. Such adjuvants commonly used in the art canbe found in the John W. McCutcheon, Inc. publication "Detergents andEmulsifiers, Annual." Allured Publishing Co., Ridgewood, N.J.

In general, the compounds of this invention can be dissolved in certainsolvents such as acetone, methanol, ethanol, dimethylformamide, pyridineor dimethyl sulfoxide and such solutions can be extended with water. Theconcentrations of the solution can vary from about 1% to about 90% witha preferred range being from about 5% to about 50%.

For the preparation of emulsifiable concentrates, the compound can bedissolved in suitable organic solvents, or a mixture of solvents,together with an emulsifying agent with permits dispersion of thefungiride in water. The concentration of the active ingredient inemulsifiable concentrates is usually from about 10% to about 90% and inflowable emulsion concentrates, this can be as high as about 75%.

Wettable powders suitable for spraying, can be prepared by admixing thecompound with a finely divided solid, such as clays, inorganic silicatesand carbonates, and silicas and incorporating wetting agents, stickingagents, and/or dispersing agents in such mixtures. The concentration ofactive ingredients in such formulations is usually in the range fromabout 20% to about 98%, preferably from about 40% to about 75%.

A water dispersible granular product may be obtained by granulating oragglomerating a suitable wettable powder formulation that is compatiblewith the active ingredients. Agglomeration may be. carried out by anyconvention method such as pan agglomeration. Illustrative waterdispersible granules are described in U.S. Pat. No. 3,954,439.

Dusts are prepared by mixing the heterocyclic acetonitriles,enantiomorphs, salts and complexes thereof with finely divided inertsolids which can be organic or inorganic in nature. Materials useful forthis purpose include botanical flours, silicas, silicates, carbonatesand days. On convenient method of preparing a dust is to dilute awettable powder with a finely divided carrier. Dust concentratescontaining from about 20% to about 80% of the active ingredient arecommonly made and are subsequently diluted to from about 1% to about 10%use concentration.

The heterocyclic acetonitriles, enantiomorphs, salts and complexesthereof can be applied as fungitidal sprays by methods commonlyemployed, such as conventional high-gallonage hydraulic sprays,low-gallonage sprays, air-blast spray, aerial sprays and dusts. Thedilution and rate of application will depend upon the type of equipmentemployed, the method of application and diseases to be controlled, butthe preferred effective amount is usually from about 0.1 lb. to about 50lbs. per acre of the active ingredient.

As a seed protectant, the amount of toxicant coated on the seed isusually at a dosage rate of from about 0.1 to about 20 ounces perhundred pounds of seed. As a soil fungiride the chemical can beincorporated in the soil or applied to the surface usually at a rate offrom about 0.1 to about 50 lbs. per acre. As a foliar fungiride, thetoxicant is usually applied to growing plants at a rate of from about0.25 to about 10 lbs. per acre.

Fungirides which can be combined with the fungirides of this inventioninclude:

(a) dithiocarbamate and derivatives such as: ferbam, ziram, maneb,mancozeb,zineb, propineb, metham, thiram, the complex of zineb andpolyethylene thiuram disulfide, dazomet, and mixtures of these withcopper salts;

(b) nitrophenol derivatives such as: dinocap, binapacryl, and2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate;

(c) heterocyclic structures such as: captan, folpet, glyodine,anilazine, ditalimfos, 4-butyl-1,2,4-triazole,5-amino-1-[bis(dimethylamino)phosphinyl]-3-phenyl-1,2,4-triazole,etradiazole, dithianon, thioquinox, benomyl, thiabendazole,4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, vinclozolin,iprodione, procymidone, triadimenoI, triadimefon, bitertanol,prochloraz, fenasimol, bis-(p-chlorophenyl)-3-pyridinemethanol,bis-(p-chlorophenyl)-5-pyrimidinemethanol, triarimol,flutriafol,flusilazole, propiconazole, etaconazole, mydobutanil,alpha-[2-(4-chlorophenyl)ethyl]-alpha-phenyl-1H-1,2,4-triazole-1-propanenitrile,hexaconazole, cyproconazole, terbuconazole, diniconazole, fluoroimide,pyridine-2-tkiol-1-oxide, 8-hydroxyquinoline sulfate and metal saltsthereof, 2,3-dihydro-5-carboxyanilido-6-methyl-1,4-oxathiin-4,4-dioxide,2,3-dihydric>-5-carboxyanilido-6-methyl-1,4-oxathiin,cis-N-[(1,1,2,2-tetrachloroethyl)thiol]-4-cyclohexene-1,2-dicarboxirnide,cydoheximide, dehydroacetic add, captafol, ethirimol, quinomethionate,D,L-methyl-N-(2,6-dimethylphenyl)-N-(2'-methoxyacetyl)alanine methylester,D,L-methyl-N-(2,6-dimethylphenyl)-N-chloroacetyl-D,L-2-aminobutyrolactone,D,L-N-(2,6-dimethylphenyl)-N-(phenylacetyl)alanine methyl ester,5-methyl-5-vinyl-3-(3,5-dichlorophenyl)-2,4-dioxo-1,3-oxazolidine,3-(3,5-dichlorophenyl)-5-methyl-5-(methoxymethyl)-1,3-oxazolidi-2,4-dione,3-(3,5-dichlorophenyl)-1-isopropylcarbamoylhydantoin,2-cyano-[N-(ethylaminocarbonyl)-2-methoximino]acetamide, fenpropimorph,fenpropidine, 2,6-dimethyl-N-tridecylmorpholine, dodemorph, andtriforine;

(d) miscellaneous halogenated fungirides such as: chloranil, dichlone,chloroneb, tricamba, TCPN, dichloran, 2-chloro-1-nitropropane,polychloronitrobenzenes such as pentachloronitrobenzene (PCNB), andtetrafluorodichloroacetone;

(e) fungitidal antibiotics such as: griseofulvin, kasugamydn, polyoxin,validamycin, and streptomycin;

(f) copper-based fungirides such as: copper hydroxide, cuprous oxide,basic cuptic chloride, basic copper carbonate, copper terephthalate,copper naphthenate and Bordeaux mixture; and

(g) miscellaneous fungirides such as: dodine, phenylmercuric acetate,N-ethylmercuri-1,2,3,6-tetrahydro-3,6-endomethano-3,4,5,6,7,7-hexachlorophthalimide,phenylmercuric monoethanol ammonium lactate, p-dimethylaminobenzenesodium sulfonate, methyl isothiocyanate, 1-thiocyano-2,4-dinitrobenzene,1-phenyl thiosemicarbazide, nickel-containing compounds, calciumcyanamide, lime sulfur, thiophanate-methyl, flutolanil, edinophos,isoprothiolane, propenazoie, and tricyclazole.

The heterocyclicacetonitriles enantiomorphs, add addition salts andmetal salt complexes of this invention can be advantageously employed invarious ways. Since these compounds possess broad spectrum fungitidalactivity, they can be employed in the storage of cereal grain. Thesecomplexes can aim be employed as fungirides in turf, fruit and nutorchards, vegetables and golf course applications. Other applications ofthe compounds of this invention will suggest themselves to those skilledin the art of agriculture and horticulture.

The compounds of the present invention have fungitoxic activity,providing control of a broad spectrum of phytopathogenic fungi includingthose in the classes of Deuteromycetes (Fungi Imperfecti), Oomycetes,Basidiomycetes and Ascomycetes. More particularly, the method of thisinvention provides for control of organisms which cause diseases on manycrops including such important genera as Erysiphe, Pucdnia,Leptoshaeria, Thanatephorus, Pyricularia, Phytophthora, PIasmopara,Altemaria, Guignardia, Pseudocercosporella, Venturia, Monilinia, andUstilago. More particularly, wheat diseases including powdery mildew(Erysiphe graminis), leaf rust (Puccinia recondita), stem rust (Pucciniagraminis f.sp. tritici) and septoria leaf and glume blotch (LeptoshaeHanodomm) are controlled by the method of the invention. Other diseasescontrolled include cercospora leaf spots (Mycosphaerella arachidis andCercospora beticola), botrytis diseases (Botryotinia fuckelioniana),helminthosporium diseases (Cochliobolous toiyabeanus, Cochlioboloussativus, Cochliobolus heterostrophus), rice blast (Magnaporthe grisea)and alternaria bright (Alternaria solani). Consequently, variouscompounds of this invention may be useful in treating fungi which mayaffect cereal, fruit, nut, vegetable, feed and fiber crops.

The following examples are provided merely as illustrations and are notto be considered as limitations or restrictions of the scope of thisinvention which is defined by the claims.

EXAMPLE 1

Preparation of 4-(4-chlorophenyl)-2-phenyl-2-(3-pyridyl)-butanenitrile(compound 1).

In a 1 liter 3 neck round bottomed flask, under N₂, was charged 7.2 g of60% NaH (1.5 eq., 0.15 moles), washed 2 times with 25 ml. hexanes in 100ml. dimethylformamide (DMF). To the base was added dropwise 25.5 g of4-(4-chlorophenyl)-2-phenylbutanenitrile (1.0 eq., 0.10 moles) in 150ml. DMF and was stirred for 45 min. at rt. This was followed by theaddition of 14.2 g of 3-bromopyridine (0.9 eq., 0.09 moles) in 75 ml. ofDMF. The mixture was then heated at 75°-80° C. for 5 hrs. at which timegas-liquid GLC analysis indicated no unreacted 3-bromo pyridineremained. The reaction was quenched by the addition of 200 ml. of H20and then extracted with 400 ml. of 1:1 EtOAc:Et2O. The ethylacetate/ether phase was washed with 250 ml. water (H₂ O)and 400 ml. of10% hydrochloric acid (HCl), dried over magnesium sulfate (MgSO₄) andconcentrated to give 29.1 g of oil. This crude product was furtherpurified via an acid/base extraction. The crude product was dissolved in300 ml. of toluene to which 300 ml. of 25% sulfuric acid (H₂ SO₄) wasadded which resulted in separation of an oil. To the oil and add wasadded 300 ml of ethyl acetate (EtOAc) which was neutralized with 50%sodium hydroxide (NaOH) to a pH of 10. This was washed with H₂ O (2×300ml.), dried and concentrated to give 18.2 g of oil which solidified.Trituration with 40 ml. of isopropanol gave 13.0 g of a white solid, mp83°- 84° C. (43.4% yield).

    ______________________________________                                        C.sub.21 H.sub.17 N.sub.2 Cl                                                           C    H           N      Cl                                           ______________________________________                                        Theor:     75.79  5.11        8.42 10.68                                      Found:     74.69  5.22        8.24 11.14                                      ______________________________________                                    

EXAMPLE 2

Preparation of4-(4-chlorophenyl)-2-phenyl-2-(5-pyrimidinyl)butanenitrile (Compound 2)

In a 250 ml. 3 neck round bottomed flask under nitrogen was charged 1.2g of 60% NaH (1.5 eq., 0.0293 moles), washed 2 times with 15 ml.hexanes, in 40 ml. DMF. Dropwise was added 5.0 g. of4-(4-chlorophenyl)-2-phenylbutanenitrile (1.0 eq., 0.0195 moles) in 10ml. of DMF and was stirred for one hour at rt. This was followed by theaddition of 4.67 g. of 5-bromopyrimidine (1.5 eq., 0.0293 moles) in 10ml. of DMF to the reaction mixture which resulted in an exotherm to 35°C. After 45 min. GLC analysis showed no unreacted nitrile. The reactionwas quenched by the addition of 100 ml. Water and then extracted with250 ml. EtOAc. The organic phase Was washed with 2 times 100 ml. water,dried over MgSO₄ and concentrated to give 7.3 g. of oil. 6.0 g. of crudeproduct was purified by flash chromatography with 3:7 EtOAc/hexane togive 2.3 g. of a white solid mp. 89°-91° C. (43.1% based onchromatographic portion).

    ______________________________________                                        C.sub.20 H.sub.l6 N.sub.3 Cl                                                           C    H           N      Cl                                           ______________________________________                                        Theor:     71.96  4.80        12.59                                                                              10.64                                      Found:     72.39  5.02        12.48                                                                              10.57                                      ______________________________________                                    

NMR (200 MHz)): 2.6-2.7(s, 4H), (9H), 8.8(s, 2H), and 9.2-(s, 1H).

EXAMPLE 3

Preparation of alpha-4-fluorophenyl-3-pyridylacetonitrile

In a 1 liter 3 neck round bottomed flask was charged 20.0 g. of4-fluorobenzyl cyanide (1.0 eq., 0.15 moles), in 300 ml.dimethylsulfoxide (DMSO) (dried over molecular sieves), and 46.8 g. of3-bromopyridine (2.0 eq., 0.30 moles) while stirring under N₂. Thereaction mixture was heated to 60° C. at which time 12.4 g of KOH (1.5eq., 0.22 moles) as powdered pellets was added neat. The reactionexotherms to 80° C. and was monitored by GLC. After 30 min., anadditional 2.4 g. of potassium hydroxide (KOH) was added (0.3 eq., 0.043moles) and 1 hr. later GLC showed 6% unreacted nitrile. The reaction wasquenched by the addition of 500 ml. of water and then extracted with 1liter of ether. The organic phase was washed 3 times 250 ml. H₂ O, driedover MgSO₄ and concentrated to give 50 g. of oil. The crude product wasdistilled under vacuum to give 15.7 g. of oil (49.4% yield) bp 160°-170°C. @1-2 min. Hg.

NMR (200 MHz): 5.2(s, 1H), 7.0-7.4 (m, 5H), 7.6-7.8 (m, 1H), and 8.5-8.6(m, 2H).

EXAMPLE 4

Preparation 2-(4-fluorophenyl)-4-phenyl-2-(3-pyridyl)butanenitrile(Compound 28).

In a 300 ml. 3 neck round bottomed flask under N₂ was charged 0.9 g. of60% NaH (1.5 eq., 0.0225 moles), washed 2 times with 15 ml hexartes, in40 ml. DMF and 5.5 g. of 2-bromoethylbenzene (2.0 eq., 0.030 moles).This was followed. by the addition of 3.18 g. ofalpha-4-fluorophenyl-3-pyridylacetonitrile (1.0 eq., 0.015 moles) in 10ml. DMF which resulted in an exotherm to 46° C. After 15 min. GLCanalysis showed no unreacted nitrile. The reaction was quenched by theaddition of 100 ml. water and then extracted with 250 ml. ether. Theorganic phase was washed twice with 100 ml. water, dried over MgSO₄ andconcentrated to give 5.0 g. of oil. The crude product was purified byflash chromatography with 2:3 EtOAc/hexane to give 3.7 g. of an oil(78.0% yield).

    ______________________________________                                        C.sub.21 H.sub.17 N.sub.2 F                                                            C    H           N      F                                            ______________________________________                                        Theor:     79.75  5.38        8.86 6.41                                       Found:     78.50  5.18        8.54 6.09                                       ______________________________________                                    

NMR (200 MHz): 2.6-2.8(s,4H), 7.0-7.5(m, 10H), 7.7-7.8(m, 1H), and8.5-8.7 (m, 2H).

EXAMPLE 5

Preparation of 4-chlorophenethyl Zbromide

A 500 ml. 3 neck round bottomed flask under nitrogen was charged 15.65g. of 4-chlorophenethanol (1.0 eq., 0.10 moles) in 60 ml. toluene. Tothe reaction was added dropwise 41.6 g of thionyl bromide (2.0 eq., 0.20moles) in 15 ml. of toluene maintaining the temp. below 25 C. Finally,8.7 g. pyridine (1.1 eq., 0.11 moles) in 20 ml. toluene was addeddropwise again keeping the temperature below 30° C. with an external icebath. The reaction was monitored by GLC and after 1 hr. an additional14.0 g of thionyl bromide (0.67 eq. 0.067 moles) was added followedthree hours later by 9.7 gms. (1.1eq., 0.11;moles). Subsequently 4.3 g.of pyridine was added (0.55 eq., 0.055 moles) after which GLC indicatedall the alcohol was consumed. The reaction was quenched by the additionof 300 ml of water while cooling with an ice bath after which 400 ml. ofether was added. The ether was washed water three times with 250 ml.),dried over MgSO₄ and concentrated to give 14.4 g of product as an oil(65.2% yield).

NMR (60 MHz): 2.9-3.7 (m, 4H) and 7.0-7.4 (ABq, 4H).

EXAMPLE 6

Preparation of 4-(4-chlorophenyl)-2-(2-fluorophenyl)-butanenitrile

To a 5L 4-neck round bottomed flask under a nitrogen atmosphere wascharged 93.4 g., 60% sodium hydride (1.05 equiv., 2.33 moles) thismixture was washed with hexane, and then added 340 ml. DMF was added.Then 300 g. of 2-fluorophenylacetonitrite (1.0 equiv. 2.22 moles) wasadded dropwise maintaining solution temperature at 30° C. with an icebath. After string for one hour 250 ml., toluene was added to thereaction mixture followed by dropwise addition in 3 equal portions, 532g. 4-chlorophenethyl mesylate (1.02 equiv. 2.27 moles) in 340 ml.toluene/340 ml. DMF solution. The reaction solution temperature wasmaintained <30° C. during the 1.5 hour addition. 250 ml. of toluene wasadded to the reaction after each of the three portions of mesylate wasadded to avoid solidification. Reaction progress was monitored by GLCanalysis. After stirring 3 hours, the reaction solution was poured into3L of 2% HCl solution. The phases were separated and the aqueous phasefurther extracted with two times one liter portion of ether. The organicextractions were combined and washed with two times with one Liter of ofwater followed by 1 L of brine, dried over anhydrous magnesium surface,filtered and concentrated in vacuo to give 596 g. oil. The oil wasdistilled at 150 ° C. (0.1 mm Hg.) to give 305.2 g. oil (50.3%) NMR (200MHz): 2.1-2.3 (m, 2H), 2.7-2.9 (m, 2H), 4.0-4.1 (t, 1H), 7.0-7.5 (m,8H).

EXAMPLE 7

Preparation of4-(4-chlorophenyl)-2-(2-fluorophenyl)-2-(3-pyridyl)butanitrile (Compound26)

A 5 L 4-neck round bottomed flask was charged under a nitrogenatmosphere with 104 grams of 60% sodium hydride (1.3 equiv. 2.6 moles),washed with hexanes, and then 1 L of DMF was added. To this mixture wasadded dropwise 547 grams4-(4-chlorophenyl)-2-(2-fluorophenyl)-butanenitrile (1.0 equiv., 2.0moles) in 600 ml. DMF causing an exotherm to 41° C. The reaction mixturewas stirred for one hour after which 348 grams 3-bromopyridine (1.1equiv., 2.2 moles) in 400 ml. DMF. was added dropwise to the reactionmixture. The reaction was heated at 70° C. and progress monitored by GLCanalysis. After 12 hours, 20 g. more of 3-bromopyridine (0.13 moles) wasadded and heated at 70° C. for 4 hours. After cooling to ambient,temperature, the reaction solution was poured into 7 L of water andextracted with 1.5 L of ethyl acetate. The aqueous phase was thenextracted further with 2×1 L ethyl acetate/ether 1:1 solutions. Theextractions were combined and washed with 2×1 L water portions followedby a 500 ml. brine wash. The organic phase was dried over anhydrousmagnesium sulfate, filtered, treated with charcoal, filtered throughcelite, and concentrated in vacuo. The oil was dissolved in a minimalamount of ether to which hexane was added until the solution was turbid.Solid formed while stirring for 2 days. The solid was filtered and thentriturated with hexane/2-propanol to give 317 grams of a tan solid(45.2% yield), m.p. 90°-92° C.

I.R. (nujol): EO (C.tbd.N)cm⁻¹ NMR (200 MHz): 2.5-3.0 (m, 4H),7.0-7.5(m, 8H), 7.6-7.8(m, 2H), 8.5-8.7 (m, 2H)

    ______________________________________                                        Elemental Analysis: C.sub.21 H.sub.16 N.sub.2 ClF                             C              H      N         CL   F                                        ______________________________________                                        Theor:  71.90      4.56   7.99    10.13                                                                              5.42                                   Found:  71.86      4.64   7.92    10.18                                                                              5.19                                   ______________________________________                                    

EXAMPLE 8

Preparation of4-(4-chlorophenyl)-2-(2-fluorophenyl)-2-(5-pyrimidyl)butanenitrile(Compound 41)

A 1 L 4-neck flask under a nitrogen atmosphere was charged with 4.4 g.of 60% sodium hydride (1.1 equiv., 0.11 moles), and washed with hexanes,in 75 ml. DMF. Then over 30 minutes, 27.3 g. of4-(4-chlorophenyl)-2-(2-fluorophenyl)butanenitrile (1.0 equiv., 0.10moles) in 110 ml. DMF was added dropwise to the base causing an exothermto 30° C. After the addition was complete, the reaction mixture wasstirred for 30 minutes. Over 5 minutes 17.5 g. of 5-bromopyrimidine (1.1equiv., 0.11 moles) in 75 ml. DMF was added to the reaction mixturewhich was heated at 50° C. and monitored by GLC analysis. The reactionwas quenched after 2 hours by the addition of 350 ml. water andextracted with 600 ml. ethyl acetate. The organic phase was washed withthree 300 ml. portions of water, the organic phase dried over anhydrousmagnesium sulfate, and then concentrated in vacuo at 50° C. to give 34.2grams oil which solidified..The solid was with triturated with 75 ml.isopropanol, filtered, and dried to give 16.5 g. white solid (47.0%yield), m.p.=86° C.-88° C.

I.R. (nujol): 2240 (C.tbd.N) cm⁻¹ NMR (200 MHZ): 2.6-3.0 (m, 4H),7.0-7.8 (m, 8H), 8.8 (s, 2H), 9.2 (s, 1H).

    ______________________________________                                        Elemental Analysis: C.sub.20 H.sub.15 N.sub.3 ClF                             C              H      N         Cl   F                                        ______________________________________                                        Theor:  68.28      4.27   11.95   10.10                                                                              5.40                                   Found:  68.13      4.14   11.83   10.37                                                                              5.23                                   ______________________________________                                    

EXAMPLE 9

Fungiride Test Methods

The compounds of this invention were tested for fungicidal activity invivo against cucumber downy mildew (CDM), rice blast (RB), tomato earlyblight (TEB), tomato late blight (TLB), wheat stem rust (WSR), wheatlea/rust (WLR), septoria lea/and glume blotch of wheat (SNW) and wheatpowder mildew (WPM).

The compounds were dissolved Lrt a 2:1:1 mixture of water, acetone, andmethanol, sprayed onto the plants and allowed to dry the plants wereinoculated with the fungus after about 24 hours. Each test utilizedcontrol plants which were sprayed with the water, acetone, and methanolmixture and incited with the fungus. The remainder of the technique ofeach of the tests is given below and the results are reported as percentdisease control (percentages of plants treated with the compounds of thepresent invention lacking disease signs or symptoms compared to theuntreated control plants) at a given compound dosage in parts permillion.

Cucumber Downy Mildew (CDM):

Pseudoperonospora cubensis was maintained on leaves of live Marketercucumber plants in a constant temperature room at 65° F. to 75° F. inhumid air with moderate light intensity for 7 to 8 days. A watersuspension of the spores from infested leaves was obtained and the sporeconcentration was adjusted to about 100,000 per ml. of water.

Marketer cucumber seedlings were inoculated by spraying the underside ofthe leaves with a DeVilbiss atomizer until small droplets were observedon the leaves. The inoculated plants were incubated in a mist chamberfor 24 hours at about 70° F. and then subsequently incubated for 5 to 6days in a controlled temperature room at 65° F. to 75° F. Six days afterinoculation, the percent disease control was determined.

Rice Blast (RB):

Two week old M201 rice pints were inoculated with 2.5×10⁵ sposes per potof Magnaporthe grisea (Pyricularia oryzae) by spraying the leaves andstems with a DeVilbiss atomizer. The inoculated plants were incubated ina humid environment at 80° F. for about 24 hours, then placed in agreenhouse environment (70° F. to 75° F.). Six to seven days afterinoculation, the percent disease control was determined.

Tomato Early Blight (TEB):

Alternaria solani spores were obtained from V-8 juice agar without CaCO₃for inoculation of San Marzano cultivar tomato seedlings grown for about18 days under greenhouse conditions. Plants were incubated in a mistchamber at 75° F. for 24 hours after inoculation with a DeVilbissatomizer. Plants were evaluated for disease control four days afterinoculation by comparison to standard area diagrams.

Tomato Late Blight (TLB):

Phytophthora infestaris was cultured on V8 juice plus CaCO₃ agar forthree to four weeks. The spores were washed from the agar with water anddispersed by DeVilbiss atomizer over three week old Pixie tomato platswhich had been sprayed previously with experimental fungirides. Theinoculated plants were placed in a humidity cabinet at 70° F. andconstant mist for 24 hours for infection. The pints were then removed tothe controlled environment room (65°-70° F.) and after five days diseasecontrol levels were evaluated.

Wheat Leaf Rust (WLR) and Wheat Stem Rust (WSR).

Puccinia recondita f.sp. tritici (Races PKB and PLD) was increased onseven day old wheat (cultivar Fielder) over a 14 day period in thegreenhouse. Puccinia graminios F. tritici was increased on Tylercultivar wheat seedlings in a similar manner. Spores were collected fromthe leaves with a cyclone vacuum or by settling on aluminum foil (andstored or used fresh). A spore suspension was prepared by adding 20 mg.(urediospores) per. ml. of Soltrol oil. The suspension was dispensedinto gelatin capsules (0.7 ml. capadty) which attach to the oilatomizers. One capsule is used per flat of twenty of the two inch squarepots of seven day old Fielder wheat. inoculated plants were placed in amist cabinet at 68° F. for 24 hours. Disease control levels wereevaluated eleven days after inoculation.

Wheat Powdery Mildew (WPM):

Erysiphe graminis (f. sp. tritici) was cultured on Hart wheat seedlingsin a controlled temperature room at 65° F. to 75° F. Mildew spores wereshaken from the culture plants onto Hart wheat seedlings which had beensprayed previously with the fungitidal compound. The inoculatedseedlings were kept in a controlled temperature room at 65° F. to 75° F.and subirrigated. The percent disease control was rated 8 to 10 daysafter the inoculation.

Wheat Glume Blotch: Septoria nodorum, (SNW):

A. Innoculum Production:

Multiple culture isolates from representative wheat growing areas (forexample S74-20A; S76-8 and S80-509 from the University of Georgia,Athens, Ga.) were used in the screen to insulate against failure,avirulence or narrow germ plasm of any one of the isolates. The isolateshad a color range from pink to dark gray black on the Czapek-Dox V8agar.

Pieces of inoculum from the leading edge of the colony from 2 or 3 weekold plates were placed on Czapek-Dox V-8 plates.

These were incubated from 48-72 hours in the dark at 20° C. and thenplaced in growth chambers at 20° C. with alternating light and dark12h:12h for approximately three weeks.

B. Inoculation:

One hundred mls per 10-15 plates of deionized water was poured intoone-half gallon jars; then the portion of the plate with the fungalmaterial was exdsed from the plate and dropped in the jar. Ten to totwenty plates were placed in each jar and shaken vigorously for 15-30seconds and allowed to stand for 5-10 minutes.

The spore concentration was then filtered with cheesecloth and dilutedto the appropriate concentration. Thirty to forty plates make about 1liter of diluted inoculum. A spore concentration of about 3.0×10⁶ per mlwas used.

A water agar spore germination test was conducted with each batch ofinoculum. A drop of inoculum was spread over the surface of the plateand allowed to germinate for 24 hrs. The germination percentage wasusually between 60-80%.

One week old Fielder wheat plants were used for disease evaluations.Twenty pots per flat were arranged with untreated controls in oppositecomers of each flat. One half (1/2) the volume of a Devilbis atomizer(about 22 mls) of inoculum was then sprayed on each flat. Each flat wasrotated midway through the inoculation to insure uniform distributedconidia on leaves.

The flats were air dried about 10-15 minutes and then placed in cabinetswhich had a temperature of 20° C., 12 hr:12 hr light/dark and 100%humidity. The wheat plants were incubated in these cabinets for 96 hrs.and then transferred to a Conviron chamber for disease development for 8days at 20° C. with a daytime humidity of 90% and relative humidity atnight.

C. SNW Disease Rating Protocol

Disease assessment was as follows:

The disease was evaluated 10 days following inoculation.

C=no lesions or flecks visible

99=clear leaf with 1-2 flecks

95=flecking visible, but no lesions visible

90=flecking with 1-2 tiny lesions/pot of plants

80=some leaf tip necrosis, flecklug and 1-5 lesions/leaf

50=lesions with 1/4 leaf necrosis

0=abundant lesions with leaf necrosis

Table HI shows the fungitidal activity of the exemplary compounds. TableIV gives elemental analysis of selected examples.

                                      TABLE III                                   __________________________________________________________________________    Fungicidal Activity ppm/% Control                                             Number                                                                             CDM  RB  TEB  TLB   WLR WPM  SNW*                                                                              WSR                                     __________________________________________________________________________     1   100/85                                                                             200/70                                                                            100/0                                                                              100/0 100/95                                                                            100/99                                                                             100/95                                                                             100/100                                 2   0    100/90                                                                             200/88                                                                            100/0 200/95                                                                            200/99                                                                             200/95                                                                            --                                       3   100/0                                                                              100/80                                                                            100/0                                                                               100/95                                                                             100/0                                                                              100/100                                                                           100/0                                                                             100/90                                   4    100/100                                                                           100/0                                                                             100/0                                                                              100/0 100/0                                                                              100/100                                                                           100/90                                                                            100/90                                   5   100/70                                                                             100/0                                                                             100/0                                                                              100/0 100/0                                                                              100/100                                                                           400/90                                                                            100/75                                   6   100/0                                                                              100/50                                                                            100/0                                                                              100/0 100/0                                                                              100/100                                                                           100/50                                                                            --                                       7   --   200/50                                                                            100/0                                                                               200/85                                                                             200/0                                                                              200/100                                                                           100/0                                                                             100/50                                   8   200/95                                                                             200/0                                                                             --    200/80                                                                             200/50                                                                            100/90                                                                             --  --                                       9   100/70                                                                             200/0                                                                             100/0                                                                              100/0 200/80                                                                             200/100                                                                           100/50                                                                             100/100                                10   100/70                                                                             200/0                                                                             100/0                                                                              100/0 200/80                                                                            200/99                                                                             100/80                                                                            100/90                                  11   100/70                                                                             200/0                                                                             100/0                                                                              100/0 200/0                                                                             200/95                                                                             --  100/90                                  12   200/85                                                                             200/90                                                                             100/88                                                                            200/0 200/99                                                                             200/100                                                                           200/90                                                                            100/90                                  13   200/50                                                                             200/50                                                                             100/98                                                                             200/90                                                                             200/95                                                                             200/100                                                                           200/50                                                                             100/100                                14   200/85                                                                             200/50                                                                            --    200/50                                                                             200/25                                                                            200/99                                                                             25/0                                                                              100/75                                  15   200/85                                                                             200/50                                                                            100/0                                                                              200/0 200/95                                                                             200/100                                                                           100/80                                                                            100/90                                  16   200/85                                                                             200/0                                                                              100/50                                                                            200/0 200/50                                                                            200/99                                                                             200/90                                                                            100/0                                   17   200/0                                                                              200/50                                                                            200/0                                                                              200/0 200/50                                                                            200/99                                                                             100/0                                                                             100/75                                  18   100/0                                                                              200/75                                                                            200/0                                                                              600/0 600/75                                                                            600/75                                                                             100/0                                                                             100/0                                   19   --   200/0                                                                             200/0                                                                               600/100                                                                            600/0                                                                             600/75                                                                             --  --                                      20   --   200/90                                                                            200/0                                                                              600/0 600/50                                                                            600/75                                                                             --  --                                      21   200/0                                                                              200/0                                                                             200/0                                                                              600/0 600/0                                                                             200/50                                                                             --  --                                      22   200/0                                                                              200/0                                                                             200/0                                                                               200/80                                                                             200/25                                                                             200/100                                                                           200/0                                                                             --                                      23   200/95                                                                             200/50                                                                            200/0                                                                              600/0 600/50                                                                            600/0                                                                              --  --                                      24   200/0                                                                              200/99                                                                             200/50                                                                             200/100                                                                            200/0                                                                              200/100                                                                           --  --                                      25   200/0                                                                              200/75                                                                            200/0                                                                               200/80                                                                             200/25                                                                            200/95                                                                             --  --                                      26   200/95                                                                             200/50                                                                             200/50                                                                            200/0 200/25                                                                            200/99                                                                             --  --                                      27   200/95                                                                             200/50                                                                            200/0                                                                              200/0 200/25                                                                            200/99                                                                             100/0                                                                             100/0                                   28   200/0                                                                              200/75                                                                            --   200/0 200/0                                                                              200/100                                                                           --  --                                      29   200/50                                                                             200/0                                                                             100/0                                                                              200/0 200/0                                                                             200/99                                                                             200/80                                                                            --                                      30   200/0                                                                              200/75                                                                             200/75                                                                            200/0 200/90                                                                             200/100                                                                           200/90                                                                            100/99                                  31   200/50                                                                             200/0                                                                             200/0                                                                              200/0 200/50                                                                            200/75                                                                             --  --                                      32   200/90                                                                             200/0                                                                              200/75                                                                            200/0 200/0                                                                              200/100                                                                           100/50                                                                             100/100                                33   200/50                                                                             200/0                                                                             200/0                                                                              200/0 200/99                                                                            200/99                                                                             100/50                                                                            100/90                                  34   200/70                                                                             200/75                                                                             200/88                                                                            200/0 200/0                                                                              200/100                                                                           100/0                                                                             100/0                                   35   200/0                                                                              200/0                                                                              200/50                                                                            200/0 200/80                                                                            200/95                                                                             200/90                                                                            --                                      36   200/0                                                                              200/0                                                                              200/50                                                                             200/50                                                                             200/80                                                                            200/99                                                                             100/50                                                                            100/99                                  37   200/80                                                                             200/90                                                                            200/0                                                                               200/70                                                                             200/50                                                                            200/85                                                                             --  --                                      38   200/85                                                                             200/90                                                                            200/0                                                                               200/85                                                                             200/0                                                                              200/100                                                                           --  --                                      39   200/95                                                                             200/75                                                                            200/0                                                                               200/85                                                                             200/50                                                                             200/100                                                                           --  100/0                                   40   200/80                                                                             200/75                                                                            200/0                                                                              200/0 200/0                                                                             200/95                                                                             --  --                                      41   200/0                                                                              200/0                                                                              200/98                                                                            200/0 200/90                                                                            200/95                                                                             200/95                                                                            200/99                                  42   200/95                                                                             200/0                                                                             200/0                                                                               200/85                                                                             200/90                                                                            200/99                                                                             200/95                                                                            --                                      43   200/70                                                                             200/0                                                                             200/0                                                                              200/0 200/0                                                                             200/99                                                                             200/80                                                                            200/99                                  44   200/70                                                                             200/0                                                                             200/0                                                                               200/70                                                                             200/90                                                                            200/99                                                                             200/80                                                                            200/90                                  45   200/0                                                                              200/50                                                                             200/75                                                                              200/90                                                                            200/90                                                                            200/99                                                                             200/90                                                                            200/90                                  46   200/0                                                                              200/0                                                                             200/0                                                                               200/85                                                                             200/80                                                                            200/99                                                                             200/90                                                                            200/90                                  48   200/0                                                                              --   200/50                                                                            200/0 200/95                                                                             200/100                                                                           200/80                                                                            200/99                                  49   200/0                                                                              --   200/50                                                                            200/0 200/90                                                                             200/100                                                                           200/90                                                                            200/99                                  50   200/0                                                                              --   200/50                                                                            200/0 200/90                                                                            200/99                                                                             200/50                                                                             200/100                                51   200/0                                                                              --  200/0                                                                              200/0 200/90                                                                            200/99                                                                             200/80                                                                             200/100                                52   200/50                                                                             --  200/0                                                                              200/0 200/50                                                                            200/99                                                                             200/50                                                                            200/90                                  53   200/0                                                                              --  200/0                                                                              200/0 200/0                                                                             200/99                                                                             200/50                                                                            200/99                                  54   200/50                                                                             --  200/0                                                                               200/80                                                                             200/99                                                                            200/99                                                                             200/50                                                                            200/99                                  55   200/95                                                                             --   200/90                                                                            200/0 200/75                                                                            200/95                                                                             200/80                                                                            --                                      56   200/95                                                                             --   200/85                                                                            200/0 200/0                                                                             200/95                                                                             200/0                                                                             --                                      57   200/0                                                                              --  200/0                                                                              200/0 200/85                                                                            200/75                                                                             200/0                                                                             --                                      59   200/75                                                                             --  200/0                                                                              200/0 200/75                                                                             200/100                                                                           200/90                                                                            --                                      60   200/25                                                                             --   200/90                                                                            200/0 200/0                                                                             200/99                                                                             200/90                                                                            --                                      61   200/50                                                                             --  200/0                                                                              200/0 200/0                                                                             200/90                                                                             200/50                                                                            --                                      62   200/50                                                                             --  200/0                                                                              200/0 200/0                                                                             200/90                                                                             200/80                                                                            --                                      63   200/0                                                                              --   200/75                                                                            200/0 200/50                                                                            200/95                                                                             200/0                                                                             --                                      67   200/85                                                                             --  200/0                                                                              200/0 200/0                                                                             200/85                                                                             200/0                                                                             --                                      68   200/50                                                                             --  200/0                                                                              200/0 200/0                                                                             200/90                                                                             200/0                                                                             --                                      __________________________________________________________________________     *See Example 9 for SNW rating scale.                                     

                  TABLE IV                                                        ______________________________________                                                     Elemental Analyses                                               Cmpd. Empirical    Calcd./Found                                               No.   Formula      C      H    N    Cl   F    Br                              ______________________________________                                         8    C.sub.21 H.sub.16 N.sub.2 ClF                                                              71.90  4.56  7.99                                                                              10.13                                                                               5.42                                                   69.94  4.45  7.62                                                                              11.47                                                                               5.27                                 9    C.sub.22 H.sub.16 N.sub.2 ClF.sub.3                                                        65.92  4.00  6.99                                                                               8.86                                                                              14.23                                                   64.75  3.75  6.73                                                                               9.51                                                                              14.08                                10    C.sub.21 H.sub.16 N.sub.2 ClF                                                              71.90  4.56  7.99                                                                              10.13                                                                               5.42                                                   69.42  4.07  7.16                                                                              12.73                                                                               4.59                                11    C.sub.21 H.sub.16 N.sub.2 Cl.sub.2                                                         68.66  4.36  7.63                                                                              19.35                                                        68.67  4.52  7.92                                                                              19.02                                     29    C.sub.21 H.sub.16 N.sub.2 ClF                                                              71.90  4.56  7.99                                                                              10.13                                                                               5.42                                                   70.90  4.20  7.54                                                                               9.81                                                                               5.04                                31    C.sub.21 H.sub.17 N.sub.2 Br                                                               66.84  4.51  7.43          21.22                                              67.80  4.52  6.87          20.68                           32    C.sub.21 H.sub.17 N.sub.2 Cl                                                               75.81  5.11  8.42                                                                              10.65                                                        74.03  5.47  8.47                                                                              10.33                                     36    C.sub.12 H.sub.16 N.sub.2 ClF                                                              71.90  4.56  7.99                                                                              10.13                                                                               5.42                                                   71.22  4.60  7.97                                                                              10.59                                                                               5.78                                57    C.sub.27 H.sub.22 N.sub.2                                                                  86.63  5.88  7.49                                                             84.37  5.82  6.94                                          59    C.sub.22 H.sub.20 N.sub.2                                                                  84.62  6.41  8.97                                                             84.20  6.48  8.95                                          61    C.sub.22 H.sub.19 N.sub.2 Cl                                                               76.19  5.48  8.08                                                                              10.24                                                        75.68  5.60  7.86                                                                              10.61                                     62    C.sub.21 H.sub.18 N.sub.3 Cl                                                               72.52  5.18 12.09                                                                              10.21                                                        72.05  5.24 12.06                                                                              10.78                                     63    C.sub.21 H.sub.18 N.sub.3 Cl                                                               72.52  5.18 12.09                                                                              10.21                                                        72.10  5.10 11.99                                                                              10.96                                     ______________________________________                                    

Although the invention has been described with regard to its preferredembodiments, which constitute the best mode presently known to theinventors, it should be understood that various changes andmodifications as would be obvious to one having ordinary skill in thisart may be made without departing from the scope of the invention, whichis set forth in the following claims.

We claim:
 1. A compound of the formula: ##STR7## wherein Ar₁ is selectedfrom an optionally substituted C₆ to C₁₀ aryl group with up to threesubstituents independently selected from the group consisting ofhalogen, nitro, cyano, (C₁ -C₁₂) alkyl, (C₁ -C₁₂) haloalkyl, (C₃ -C₈)cycloalkyl, (C₅ -C₈) cycloalkenyl, (C₂ -C₁₂) alkenyl, (C₂ -C₁₂) alkynyl,(C₁ -C₁₂) alkoxy, (C₁ -C₁₂) haloalkoxy, (C₁ -C₁₂) alkylthio, (C₁ -C₁₂)alkylsulfinyl, (C₁ -C₁₂) alkylsulfonyl, phenyl, phenoxy, phen(C₁-C₁₂)alkyl, phen(C₂ -C₁₂)alkenyl, phen(C₂ -C₁₂)alkynyl and (C₅-C₆)cycloalkyl (C₁ -C₆)alkyl; Ar₂ is an optionally substituted (C₆ -C₁₀)aryl group wherein the substitutuents are independently selected fromthe substitutents enumerated above for Ar₁ ; or Ar₂ may be thiophenyl orfuranyl; Het is a pyrimidyl ring; n is the integer 2 or 3; or theagronomically acceptable enatiomorph, acid addition salt or metalcomplex thereof.
 2. The compound of to claim 1 wherein Ar₁ and Ar₂ areindependently selected form phenyl or phenyl substituted with up to twosubstitutuents selected from the group consisting of methyl, halomethyl,halogen, and alkoxy; and Het is a pyrimidyl ring; n is the integer 2 or3; or the agronomically acceptable enatiomorph or acid salt thereof. 3.The compound of claim 1 wherein Ar₁ is phenyl or 2- or 4-halosubstitutedphenyl; Ar₂ is phenyl or 3- or 4-halosubstituted phenyl; Het is5-pyrimidyl and n is the integer
 2. 4. The compound of claim 1 whereinAr₁ is 2- or 4-chloro-, or 2-or 4-fluorophenyl; Ar₂ is 4-chloro- or4-fluorophenyl; Het is 5-pyrimidyl; and n is the integer
 2. 5. Afungicidal composition comprising a fungicidally effective amount of thecompound of claim 1 and an agronomically acceptable inert carrier.
 6. Afungicidal composition comprising a fungicidally effective amount of thecompound of claim 2 and an agronomically acceptable inert carrier.
 7. Afungicidal composition comprising a fungicidally effective amount of thecompound of claim 3 and an agronomically acceptable inert carrier.
 8. Afungicidal composition comprising a fungicidally effective amount of thecompound of claim 4 and an agronomically acceptable inert carrier.
 9. Amethod of controlling fungi comprising contacting said fungi or thelocus of said fungi with a fungicidally effective amount of a compoundof the formula: ##STR8## wherein Ar₁ is selected from an optionallysubstituted C₆ to C₁₀ aryl group with up to three substituentsindependently selected from the group consisting of halogen, nitro,cyano, (C₁ -C₁₂) alkyl, (C₁ -C₁₂) haloalkyl, (C₃ -C₈) cycloalkyl, (C₅-C₈) cycloalkenyl, (C₂ -C₁₂) alkenyl, (C₂ -C₁₂) alkynyl, (C₁ -C₁₂)alkoxy, (C₁ -C₁₂) haloalkoxy, (C₁ -C₁₂) alkylthio, (C₁ -C₁₂)alkylsulfinyl, (C₁ -C₁₂) alkylsulfonyl, phenoxy, phenyl, phen(C₁-C₁₂)alkyl, phen(C₂ -C₁₂)alkenyl, phen(C₂ -C₁₂)alkynyl and (C₅-C₆)cycloalkyl (C₁ -C₆)alkyl; Ar₂ is an optionally substituted (C₆-C₁₀)aryl group wherein the substituents are independently selected fromthe substituents enumerated above for Ar₁ ; or Ar₂ may be thiophenyl orfuranyl; Het is a pyrimidyl ring; n in the integer 2 or 3; or theagronomically acceptable enatiomorph, acid addition salt or metalcomplex thereof.
 10. The method of claim 9 wherein Ar₁ and Ar₂ areindependently selected from phenyl or phenyl substituted with up to twosubstituents selected from the group consisting of methyl, halomethyl,halogen, and alkoxy; and Het is a pyrimidyl ring; n is the integer 2 or3; or the agronomically acceptable enatiomorph or acid salt thereof. 11.The method of claim 9 wherein Ar₁ is phenyl or 2- or 4-halosubstitutedphenyl; Ar₂ is phenyl or 3- or 4-halosubstituted phenyl; Het is5-pyrimidyl and n is the integer
 2. 12. The method of claim 9 whereinAr₁ is 2- or 4-chloro-, or 2- or 4-fluorophenyl; Ar₂ is 4-chloro- or4-fluorophenyl; Het is 5-pyrimidyl; and n is the integer 2.